RRC ID 33955
Author Yamada H, Dezawa M, Shimazu S, Baba M, Sawada H, Kuroiwa Y, Yamamoto I, Kanno H.
Title Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease.
Journal Ann Neurol
Abstract Neuronal progenitor cells (NPCs) may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is low. We transduced the von Hippel-Lindau (VHL) gene into NPCs isolated from embryonic rat brain. The NPCs with the transduced VHL gene efficiently differentiated into tyrosine hydroxylase-positive neurons in vitro. NPCs with the transduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine-tyrosine hydroxylase double-labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within the host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine-induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that a sufficient number of dopaminergic neurons can develop from them to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD.
Volume 54(3)
Pages 352-9
Published 2003-9-1
DOI 10.1002/ana.10672
PMID 12953267
MeSH Animals Brain Tissue Transplantation Cell Differentiation / physiology Cells, Cultured Corpus Striatum / cytology Corpus Striatum / physiology Corpus Striatum / transplantation* Dopamine / metabolism Embryo, Mammalian Fetal Tissue Transplantation Graft Survival Humans Immunohistochemistry Ligases / genetics* Male Models, Animal Motor Activity / physiology Neurons / cytology Neurons / physiology Neurons / transplantation* Oxidopamine Parkinsonian Disorders / chemically induced Parkinsonian Disorders / therapy* Rats Rats, Sprague-Dawley Stem Cell Transplantation* Stem Cells / cytology Stem Cells / metabolism Transduction, Genetic Tumor Suppressor Proteins* Ubiquitin-Protein Ligases* Von Hippel-Lindau Tumor Suppressor Protein
IF 9.496
Times Cited 24
DNA material Ax1 CA gfp (RDB01727)